Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

脂质纳米粒-mRNA递送系统及其在嵌合抗原受体T细胞治疗中的应用

尽管嵌合抗原受体（CAR）T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效，但需要进一步优化。脂质纳米粒（LNP）-信使核糖核酸（mRNA）递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中，一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞，从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能，以进一步诱导对实体瘤的清除；另一方面，通过LNP将成纤维细胞激活蛋白（FAP）CARmRNA靶向递送至T细胞，实现体内FAP靶向的CAR-T细胞的制备，以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中，LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点，亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。     

冠状动脉慢血流的危险因素及冠状动脉病变特点的研究

目的研究冠状动脉慢血流现象(CSFP)患者的危险因素和分析累及冠状动脉病变的特点。方法回顾性收集本院2019年1月—2021年1月因疑似冠心病行冠状动脉造影术的514例患者,分析患者的临床资料、实验室指标及冠状动脉造影结果等相关资料,按照TIMI血流分级分为慢血流组(n=288)和对照组(n=226),比较两组之间的差异,并通过logistics回归分析探讨CSFP患者的危险因素。结果 (1)两组间在性别、民族、吸烟及饮酒史上存在统计学差异(P<0.05)。(2)CSFP组的血红蛋白、游离三碘甲状原氨酸、血肌酐值、血尿酸水平、空腹血糖水平和左室舒张末期大小均高于对照组(P<0.05);而CSFP组的血小板分布宽度、游离甲状腺素、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1和白蛋白水平均低于对照组(P<0.05);(3)CSFP以三支血管病变最多见,为124例(43.0%),而单支血管病变和双支血管病变病例数一样,均为82例(28.5%)。单支血管病变中最多见的是前降支67例(81.7%),其次是右冠状动脉12例(14.6%),左回旋支较少见;(4)多因素logistic回归分析发现:性别、民族、游离甲状腺素、载脂蛋白A1和白蛋白水平是CSFP患者的独立危险因素。结论 (1)男性、少数民族、游离甲状腺素、载脂蛋白A1和白蛋白水平是CSFP的独立危险因素;(2)CSFP更常见于三支冠状动脉病变组,单支冠状动脉病变者更常见于左前降支。     

Overview of Recognition and Prevention of Child Sex Trafficking in the Primary Care Setting: A Primer for Nurse Practitioners

Child sex trafficking (CST) has become a global public health crisis and is a $150 billion criminal enterprise. Nurse practitioners are key in the recognition and prevention of CST in health care settings. Evidence demonstrates that up to 80% of CST victims have had a recent health care encounter. It is the role of the NP in practice to understand risk factors, screen for CST, and educate parents and caregivers on signs of victimization and prevention.     

银杏叶制剂联合地塞米松在老年突聋治疗中对血清炎症指标的影响

目的: 探讨银杏叶制剂联合地塞米松在老年突聋治疗中对血清炎症指标的影响。方法: 按随机数字表法将我院2016年7月-2021年7月收治的102例老年突聋患者分入两组（各51例）。对照组用地塞米松治疗，治疗组加用银杏叶制剂治疗。观察两组治疗前后纯音听阈和血管内皮功能指标[超氧化物歧化酶（SOD）、脂质过氧化物（LPO）、一氧化氮（NO）]、血清炎症指标[肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、白细胞介素-6（IL-6）]，分析其疗效与不良反应。结果: 与对照组比较，治疗组总有效率更高（96.08％vs 82.35％）（χ2=4.993，P=0.025）；两组治疗后各频率点阈值均下降，且相比对照组，治疗组治疗后各频率点阈值更低（P<0.05）；治疗后两组SOD、NO水平均升高，LPO水平降低（P<0.05），且相比对照组，治疗组治疗后SOD、NO水平更高，LPO水平更低（P<0.05）；治疗后两组血清TNF-α、CRP、IL-6水平降低，且相比对照组，治疗组TNF-α、CRP、IL-6水平更低（P<0.05）；治疗组不良反应发生率5.88％，对照组为9.80％，两组比较差异无统计学意义（P=0.543，χ2=0.461）。结论: 银杏叶制剂联合地塞米松治疗老年突聋患者疗效理想，能恢复各频率点听力，安全可靠，推测改善患者血管内皮功能和炎症因子水平是其重要作用机制。     

农村老年人老化期望现状及影响因素研究

目的 了解农村老年人的老化期望现状，分析其影响因素，为针对干预提供参考。 方法 采用一般资料调查表、UCLA孤独感量表简化版、老化期望量表、简版自我感知老化量表对199名农村老年人进行问卷调查。 结果 老化期望总分为32.72±9.18，孤独感得分为15.11±3.82，自我感知老化得分为52.75±2.76；多元线性回归分析显示，性别、婚姻状况、患慢性病种数、独居、孤独感、自我感知老化及经济来源是农村老年人老化期望的影响因素（调整R2=0.612，均P＜0.05）。 结论 农村老年人的老化期望水平较低，女性、孤独、无配偶、患慢性病较多、老化态度消极及低收入人群是关注的重点。     

慢阻肺急性加重期患者延迟就医与家庭动力学的相关性研究

目的研究慢阻肺急性加重期患者延迟就医与家庭动力学的相关性,希望能够为慢阻肺急性加重期患者拟定护理措施提供科学依据。方法选取2017年1月-2019年12月我院240例诊断为慢阻肺急性加重期的患者为研究对象。根据患者入院就医的时间进行分组,时间≥24h的延迟就医的患者为观察组,时间<24h的及时就医患者为对照组。结果两组患者在文化水平、家庭年收入、在职状态、医疗保险和婚姻状况和APACHEⅡ评分比较(P<0.05)。观察组患者疾病观念、个性化、系统逻辑和家庭氛围得分比对照组高(P<0.05)。Pearman的相关性分析结果显示:慢阻肺急性加重期患者延迟就医时间与各个层面分数以及家庭动力总分呈现负相关性(P<0.05)。应变量为延迟就医为应变量,患者的一般资料为自变量,经Logistic回归分析结果表明:延迟就医的影响因素为文化水平、家庭动力评分、职业状态、家庭收入、婚姻状况和APACHEⅡ评分。结论慢阻肺急性加重期患者家庭动力总分与疾病观念、个性化、系统逻辑和家庭氛围得分与延迟就医时间呈现负相关性,患者延迟就医的影响因素是家庭动力学评分。     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

新型驱动基因融合阳性非小细胞肺癌脑转移的研究进展北大核心

肺癌是我国最常见且死亡率最高的恶性肿瘤之一,随着表皮生长因子受体(EGFR)、间变性淋巴瘤激酶(ALK)及活性氧1(ROS1)等驱动基因及其相应分子靶向药物的出现,晚期非小细胞肺癌的治疗和预后发生了革命性变化。此外,一些少见新型驱动基因融合,包括神经调节蛋白1(NRG1)、神经营养酪氨酸受体激酶(NTRK)和转染重排因子(RET),正逐渐发展成为全身性治疗选择。然而,这些罕见新型融合驱动基因在NSCLC脑转移中的作用机制,以及优化控制和预防脑转移的意义人们所知甚少。因此,本文就近几年罕见驱动基因融合在NSCLC脑转移中的研究进行综述。